Hemicyanine-based fluorescent probes: Advancements in biomedical sensing and activity-based detection

Near-infrared (NIR) fluorescent probes have revolutionized in vivo imaging by enabling the real-time detection of biomarkers for disease diagnosis and drug screening. Among these, donor-it-acceptor (D-it-A) architecture of hemicyanine dyes have gained attention for their high fluorescence quantum yield, ease in structural versatility, and good capability to construct activatable probes. Hemicyanine-based NIR activatable probes (HNAPs) leverage intramolecular charge transfer (ICT) mechanisms for precise, biomarker-responsive fluorescence activation, making them invaluable tools in preclinical and clinical research. This review highlights the principles of molecular design and applications of HNAPs for detecting key biomarkers associated with several diseases, including as skin conditions, digestive problems, cancer, inflammation, and acute organ failure. These probes enable real-time imaging with high specificity, addressing critical clinical challenges in early diagnosis and monitoring disease progression. Moreover, the translational potential of HNAPs lies in their capacity for noninvasive imaging and targeted biomarker detection, paving the way for innovations in imaging-guided diagnosis and treatment strategies. The versatility of hemicyanine scaffolds and their ability to be tailored for diverse applications underscore their unique value in bioimaging. This progress emphasizes the transformative potential of HNAPs in advancing precision diagnostics and improving clinical outcomes. We hope this review would stimulate interest among wide researchers and expedite the clinic translation for HNAPs.